ArticleCurrent biology : CB2006
Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase.
Article in Current biology : CB, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 272 papers.
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272 citing papers in PubMed, 456 citations in OpenAlex.
- Folding a broken genome: the versatile roles of cohesin in genome maintenance.Nature reviews. Genetics · 2026Review
- Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.Nature communications · 2026Article
- Cohesin promotes genomic stability by suppressing unequal sister chromatid exchange.bioRxiv : the preprint server for biology · 2026Article
- Diverse Roles of Cohesin in Chromosome Dynamics and Stem Cells.Biotech (Basel (Switzerland)) · 2026Review
- Cohesin release-factor Wapl modulates axis and chromatin structure to promote conjunction and separation of meiotic chromosomes.Cell reports · 2026Article
- Context-dependent regulation of IgH V(D)J recombination by cohesin-STAG1 and cohesin-STAG2.Nature communications · 2026Article
- Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich's ataxia.Molecular cell · 2026Article
- Cohesin cofactor dosage sets the rate of loop extrusion, rendering genome folding tunable yet vulnerable to genetic disruption.Molecular cell · 2026Article
- Organization of replicated chromosomes by DNA loops and sister chromatid cohesion.Nature reviews. Molecular cell biology · 2026Review
- Early resolution of sister chromatids during C. elegans meiosis.The Journal of cell biology · 2026Article
- The physical chemistry of interphase loop extrusion.Cell genomics · 2026Article
- Sororin locks the DNA-exit gate of cohesin to preserve sister-chromatid cohesion.Nature communications · 2026Article
- Clinical,medRxiv : the preprint server for health sciences · 2026Article
- S-phase PARylation of microprotein RSMC enhances the function of Sororin in sister chromatid cohesion.The EMBO journal · 2026Article
- The Role of HPV and Hormone in Cervical Precancer and Cancer: Molecular Pathophysiology and Cell Biology of Disease and Treatment.Oncology research · 2026Review
- Chromosome Architecture Defined by the Meiosis-Specific Cohesin in Mammalian Germ Cells.Advances in experimental medicine and biology · 2026Review
- CTCF couples long-range loop extrusion and diffusion to mediate a diverse Igκ repertoire.Nature communications · 2025Article
- Dosage sensitivity of the loop extrusion rate confers tunability to genome folding while creating vulnerability to genetic disruption.bioRxiv : the preprint server for biology · 2025Article
- CENcyclopedia: dynamic landscape of kinetochore architecture throughout the cell cycle.Nature communications · 2025Article
- Article
212 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe linkage between duplicated chromosomes (sister chromatids) is established during S phase by the action of cohesin, a multisubunit complex conserved from yeast to humans. Most cohesin dissociates from chromosome arms when the cell enters mitotic prophase, leading to the formation of metaphase chromosomes with two cytologically discernible chromatids. This process is known as sister-chromatid resolution. Although two mitotic kinases have been implicated in this process, it remains unknown exactly how the cohesin-mediated linkage is destabilized at a mechanistic level.
resultsThe wings apart-like (Wapl) protein was originally identified as a gene product that potentially regulates heterochromatin organization in Drosophila melanogaster. We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase. Depletion of Wapl from HeLa cells causes transient accumulation of prometaphase-like cells with chromosomes that display poorly resolved sister chromatids with a high level of cohesin. Reduction of cohesin relieves the Wapl-depletion phenotype, and depletion of Wapl rescues premature sister separation observed in Sgo1-depleted or Esco2-depleted cells. Conversely, overexpression of Wapl causes premature separation of sister chromatids. Wapl physically associates with cohesin in HeLa-cell nuclear extracts. Remarkably, in vitro reconstitution experiments demonstrate that Wapl forms a stoichiometric, ternary complex with two regulatory subunits of cohesin, implicating its noncatalytic function in inactivating cohesin's ability to interact with chromatin.
conclusionsWapl is a new regulator of sister chromatid resolution and promotes release of cohesin from chromosomes by directly interacting with its regulatory subunits.
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